Sphingosine-1 phosphate is stored in relatively high concentrations in human platelets, which lack the enzymes responsible for its catabolism, and it is released into the blood stream upon activation of physiological stimuli, such as growth factors, cytokines, and receptor agonists and antigens. It may also have a critical role in platelet aggregation and thrombosis and could aggravate cardiovascular diseases. On the other hand the relatively high concentration of the metabolite in high-density lipoproteins (HDL) may have beneficial implications for atherogenesis. For example, there are recent suggestions that sphingosine-1-phosphate, together with other lysolipids such as sphingosylphosphorylcholine and lysosulfatide, are responsible for the beneficial clinical effects of HDL by stimulating the production of the potent antiatherogenic signaling molecule nitric oxide by the vascular endothelium. In addition, like lysophosphatidic acid, it is a marker for certain types of cancer, and there is evidence that its role in cell division or proliferation may have an influence on the development of cancers. These are currently topics that are attracting great interest amongst medical researchers, and the potential for therapeutic intervention in sphingosine-1-phosphate metabolism is under active investigation.
Published International Patent Application No. WO 2003/062248 describes N-(benzyl)aminoalkylcarboxylates, phosphinates, phosphonates and tetrazoles as EDG receptor agonsits. Compound [3-[[[4-[5-[4-Phenyl-5-(trifluoromethyl)-2-thienyl]-1,2,4-oxadiazol-3-yl]phenyl]methyl]amino]propyl] phosphonic acid (CAS 569684-78-2) is taught in WO 2003/062248.
Published International Patent Application No. WO 2008/023783 describes the Preparation of heterocyclic moiety-containing aminoalkanoic acids as S1P1/EDG1 receptor agonists for treatment of autoimmune diseases.